The purpose of this study is to find out why women's arteries stiffen as they go through menopause, and how this is affected by estrogen loss. We believe that arteries stiffen with the loss of estrogen because of "oxidative stress," the production of molecules that can damage cells and tissues in the body, and because the arteries lose their ability to expand, or dilate.

Arterial stiffness (carotid artery compliance) during saline and ascorbic acid [ Time Frame: Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Endothelial function - brachial artery flow-mediated dilation [ Time Frame: Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment ] [ Designated as safety issue: No ]

Endothelial cell protein expression [ Time Frame: Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment ] [ Designated as safety issue: No ]

1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7

Other Name: Ganirelix

Drug: Transdermal estradiol patch

0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)

Placebo Comparator: Pre2

Premenopausal - GnRHant plus placebo

Drug: GnRHant - Ganirelix acetate

1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7

Other Name: Ganirelix

Drug: Transdermal placebo patch

Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)

Experimental: Peri1

Perimenopausal (early) - GnRHant plus estradiol

Drug: GnRHant - Ganirelix acetate

1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7

Other Name: Ganirelix

Drug: Transdermal estradiol patch

0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)

Placebo Comparator: Peri2

Perimenopausal (early) - GnRHant plus placebo

Drug: GnRHant - Ganirelix acetate

1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7

Other Name: Ganirelix

Drug: Transdermal placebo patch

Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)

Experimental: Peri3

Perimenopausal (late) - GnRHant plus estradiol

Drug: GnRHant - Ganirelix acetate

1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7

Other Name: Ganirelix

Drug: Transdermal estradiol patch

0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)

Placebo Comparator: Peri4

Perimenopausal (late) - GnRHant plus placebo

Drug: GnRHant - Ganirelix acetate

1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7

Other Name: Ganirelix

Drug: Transdermal placebo patch

Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)

Experimental: Post1

Postmenopausal - GnRHant plus estradiol

Drug: GnRHant - Ganirelix acetate

1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7

Other Name: Ganirelix

Drug: Transdermal estradiol patch

0.075mg/d starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)

Placebo Comparator: Post2

Postmenopausal - GnRHant plus placebo

Drug: GnRHant - Ganirelix acetate

1 subcutaneous injection at 0.5 mg then daily injections of 0.25 mg for 6 days (total of 7 days of injections); testing will occur on injection day 4 and day 7

Other Name: Ganirelix

Drug: Transdermal placebo patch

Starting on day 4 of the injections following testing time point two; continue for 3 days and retest (day 7)

Detailed Description:

As women get older and go through menopause, estradiol levels decrease. Also with aging, the arteries that are located around the heart get stiffer. Over time this increase in arterial stiffness can lead to a number of health problems such as high blood pressure and heart disease. In this study we want to find out if a short-term drop in estrogen levels in premenopausal and perimenopausal women can cause arteries to become stiffer, and why this happens. Additionally, in postmenopausal women, we want to find out if a short-term increase in estrogen levels causes their arteries to become more flexible (less stiff).

Arterial health (i.e., stiffness) will be examined in premenopausal, perimenopausal and postmenopausal women before and after they are given a drug called Ganirelix™ (for 7 days), which will markedly lower their reproductive hormones. After the first 4 days of taking Ganirelix™, the women will be randomly placed into 1 of 2 treatment groups to take either estrogen (0.075 mg/d skin patch) replacement or placebo for the rest of the Ganirelix treatment. This is to increase estrogen levels back to the normal level. After having the patch on for 4 days, arterial health will be examined again.

Eligibility

Ages Eligible for Study:

18 Years to 70 Years (Adult, Senior)

Genders Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Criteria

Inclusion Criteria:

Healthy women of all races and ethnic backgrounds in one of the following groups:

Perimenopausal: 40-55 years, categorized as either early (at least 2 cycles with cycle length changes of at least 7 days) or late (more than 3 months of amenorrhea) transition

Postmenopausal: 45-70 years, more than 12 months of amenorrhea as defined by the menopausal staging system (STRAW); additionally, postmenopausal women will be categorized into early and late stages as defined by the STRAW definition, specifically, women who are less than 5 years postmenopause will be considered early, and women more than 6 years will be categorized as late

All postmenopausal women will have undergone natural menopause

No oral contraceptive or Hormone Replacement Therapy (HRT) use for at least 6 months

Resting blood pressure less than 140/90 mmHg

Plasma glucose concentrations less than 110 mg/dl under fasting conditions

Sedentary or recreationally active (less than 3 days of vigorous aerobic exercise)

No use of medications that might influence cardiovascular function

Nonsmokers

No use of vitamin supplements or willing to stop use for duration of the study

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00608062

Locations

United States, Colorado

University of Colorado Anschutz Medical Center, Clinical Translational Research Center and Exercise Research Laboratory